What are the next steps in managing a 46-year-old male with hypertriglyceridemia, currently on Zetia (ezetimibe), fenofibrate, and Vascepa (icosapent ethyl), with persistent severe hypertriglyceridemia?

From the Guidelines

For a 46-year-old male with persistent hypertriglyceridemia (377 mg/dL) despite being on ezetimibe, fenofibrate, and icosapent ethyl (Vascepa), adding a moderate to high-intensity statin would be the appropriate next step. I recommend starting atorvastatin 20-40 mg daily or rosuvastatin 10-20 mg daily, as supported by the 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia 1. While the patient has shown significant improvement from the initial triglyceride level of 2108 mg/dL, the current level still exceeds the target of <150 mg/dL. Statins primarily target LDL cholesterol but also reduce triglycerides by 10-30%, working synergistically with the current medications. Before starting the statin, baseline liver function tests should be obtained, with follow-up testing in 4-12 weeks. Additionally, lifestyle modifications should be reinforced, including limiting alcohol, reducing simple carbohydrates and saturated fats, increasing physical activity, and achieving weight loss if needed.

Some key points to consider in the management of this patient include:

• The presence of persistent hypertriglyceridemia supports a decision to initiate at least moderate-intensity statin therapy, as stated in the 2021 ACC expert consensus decision pathway 1.
• Statins provide a 10% to 30% dose-dependent reduction in triglycerides in patients with elevated triglyceride levels, making them a valuable addition to the patient's current medication regimen.
• The 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk also emphasizes the importance of adherence to lifestyle modifications and evidence-based statin therapy 1.
• Older guidelines, such as the 2006 AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease, also support the use of statins in patients with elevated triglycerides, but the more recent 2021 ACC expert consensus decision pathway takes precedence in guiding management decisions 1.

Overall, the addition of a moderate to high-intensity statin to the patient's current medication regimen, along with continued lifestyle modifications, is the most appropriate next step in managing his persistent hypertriglyceridemia.

From the Research

Current Treatment and Next Steps

The patient is currently on zetia, fenofibrate, and vascepa, with triglyceride levels still at 377 mg/dL, down from 2108 mg/dL. Considering the current treatment regimen, the next steps in management could involve:

• Adding a statin to the current regimen, as statins are often used in combination with fibrates and omega-3 fatty acids to manage hypertriglyceridemia 2, 3
• Continuing to monitor and adjust the current treatment regimen, as the patient has already shown a significant reduction in triglyceride levels
• Considering alternative or additional therapies, such as niacin or other novel agents, if the patient's triglyceride levels remain elevated despite the current treatment regimen 4

Rationale for Adding a Statin

The addition of a statin to the patient's current regimen may be justified due to the following reasons:

• Statins have been shown to be effective in reducing triglyceride levels, particularly when used in combination with fibrates and omega-3 fatty acids 2, 3
• The patient's current triglyceride level of 377 mg/dL is still elevated, and the addition of a statin may help to further reduce this level
• Statins have been shown to be safe and well-tolerated in patients with hypertriglyceridemia, and can be used in combination with other lipid-lowering therapies 5, 6

Alternative Therapies

If the patient's triglyceride levels remain elevated despite the addition of a statin, alternative or additional therapies may be considered, such as:

• Niacin, which has been shown to be effective in reducing triglyceride levels and improving lipid profiles 2, 3
• Novel agents, such as apoC-III mRNA antisense inhibitors or ANGPTL3 antibodies, which are currently being investigated for the treatment of hypertriglyceridemia 4
• Other omega-3 fatty acid-based therapies, such as icosapent ethyl, which have been shown to be effective in reducing triglyceride levels and improving lipid profiles 6